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O35240

- ASIC3_RAT

UniProt

O35240 - ASIC3_RAT

Protein

Acid-sensing ion channel 3

Gene

Asic3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei26 – 261Potassium ion selectivity and permeability

    GO - Molecular functioni

    1. enterobactin transporter activity Source: Ensembl
    2. ligand-gated sodium channel activity Source: MGI
    3. PDZ domain binding Source: RGD
    4. protein binding Source: IntAct

    GO - Biological processi

    1. detection of chemical stimulus involved in sensory perception of pain Source: Ensembl
    2. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
    3. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
    4. response to acid chemical Source: Ensembl
    5. response to acidic pH Source: MGI
    6. response to heat Source: Ensembl
    7. sodium ion transmembrane transport Source: GOC
    8. sodium ion transport Source: MGI

    Keywords - Molecular functioni

    Ion channel, Sodium channel

    Keywords - Biological processi

    Ion transport, Sodium transport, Transport

    Keywords - Ligandi

    Sodium

    Enzyme and pathway databases

    ReactomeiREACT_198302. Stimuli-sensing channels.

    Protein family/group databases

    TCDBi1.A.6.1.2. the epithelial na(+) channel (enac) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Acid-sensing ion channel 3
    Short name:
    ASIC3
    Alternative name(s):
    Amiloride-sensitive cation channel 3
    Dorsal root ASIC
    Short name:
    DRASIC
    Gene namesi
    Name:Asic3
    Synonyms:Accn3, Drasic
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 4

    Organism-specific databases

    RGDi708578. Asic3.

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity; Multi-pass membrane protein By similarity
    Note: In part cytoplasmic in cochlea cells By similarity. Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4.By similarity3 Publications

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. integral component of plasma membrane Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi20 – 201V → P: No effect on selectivity or channel function. 1 Publication
    Mutagenesisi21 – 211F → S: Loss of channel function. 1 Publication
    Mutagenesisi26 – 261T → K: Alters selectivity of the channel for sodium. No effect on channel function. 1 Publication
    Mutagenesisi40 – 401T → G: Loss of regulation by PKC through PRKCABP; when associated with G-523. 1 Publication
    Mutagenesisi523 – 5231S → G: Loss of regulation by PKC through PRKCABP; when associated with G-40. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 533533Acid-sensing ion channel 3PRO_0000181303Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei40 – 401Phosphothreonine; by PKC1 Publication
    Disulfide bondi93 ↔ 187By similarity
    Disulfide bondi165 ↔ 172By similarity
    Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi283 ↔ 372By similarity
    Disulfide bondi317 ↔ 368By similarity
    Disulfide bondi321 ↔ 366By similarity
    Disulfide bondi330 ↔ 352By similarity
    Disulfide bondi332 ↔ 344By similarity
    Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
    Modified residuei523 – 5231Phosphoserine; by PKC1 Publication

    Post-translational modificationi

    Phosphorylated by PKA By similarity. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel.By similarity1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiO35240.

    PTM databases

    PhosphoSiteiO35240.

    Expressioni

    Tissue specificityi

    Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal chord and brain stem.4 Publications

    Developmental stagei

    Expression is first detected at E15.5. Strongly expressed perinatally.1 Publication

    Inductioni

    Transcriptionally regulated by the proinflamatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs.3 Publications

    Gene expression databases

    GenevestigatoriO35240.

    Interactioni

    Subunit structurei

    Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with LIN7B, MAGI1 and GOPC By similarity. Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    InadlQ63ZW7-32EBI-982374,EBI-8158524From a different organism.
    Slc9a3r1Q9JJ195EBI-982374,EBI-982391
    Slc9a3r2Q920G22EBI-982374,EBI-982439
    StomP541163EBI-982374,EBI-8004826From a different organism.

    Protein-protein interaction databases

    DIPiDIP-35759N.
    IntActiO35240. 4 interactions.
    MINTiMINT-1777886.
    STRINGi10116.ENSRNOP00000011300.

    Structurei

    3D structure databases

    ProteinModelPortaliO35240.
    SMRiO35240. Positions 41-464.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1919CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini41 – 435395ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini457 – 53377CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei20 – 4021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei436 – 45621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi530 – 5334PDZ-bindingBy similarity

    Domaini

    The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG262945.
    GeneTreeiENSGT00640000091217.
    HOGENOMiHOG000247010.
    HOVERGENiHBG004150.
    InParanoidiO35240.
    KOiK04830.
    OMAiTECHMEC.
    OrthoDBiEOG72VH5P.
    PhylomeDBiO35240.
    TreeFamiTF330663.

    Family and domain databases

    InterProiIPR004724. EnaC.
    IPR001873. Na+channel_ASC.
    IPR020903. Na+channel_ASC_CS.
    [Graphical view]
    PANTHERiPTHR11690. PTHR11690. 1 hit.
    PfamiPF00858. ASC. 1 hit.
    [Graphical view]
    PRINTSiPR01078. AMINACHANNEL.
    TIGRFAMsiTIGR00859. ENaC. 1 hit.
    PROSITEiPS01206. ASC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O35240-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV    50
    LLSLAAFLYQ VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR 100
    SRLTPNDLHW AGTALLGLDP AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL 150
    YARAGHSLED MLLDCRYRGQ PCGPENFTVI FTRMGQCYTF NSGAHGAELL 200
    TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV QIHSQDEPPA 250
    IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP 300
    LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK 350
    DCASPALDAM LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN 400
    RSESYITENV LVLDIFFEAL NYEAVEQKAA YEVSELLGDI GGQMGLFIGA 450
    SLLTILEILD YLCEVFQDRV LGYFWNRRSA QKRSGNTLLQ EELNGHRTHV 500
    PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL 533
    Length:533
    Mass (Da):59,227
    Last modified:January 1, 1998 - v1
    Checksum:i294B57322C74B3DC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013598 mRNA. Translation: AAB69328.1.
    RefSeqiNP_775158.1. NM_173135.1.
    UniGeneiRn.24225.

    Genome annotation databases

    EnsembliENSRNOT00000011300; ENSRNOP00000011300; ENSRNOG00000008380.
    GeneIDi286920.
    KEGGirno:286920.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013598 mRNA. Translation: AAB69328.1 .
    RefSeqi NP_775158.1. NM_173135.1.
    UniGenei Rn.24225.

    3D structure databases

    ProteinModelPortali O35240.
    SMRi O35240. Positions 41-464.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-35759N.
    IntActi O35240. 4 interactions.
    MINTi MINT-1777886.
    STRINGi 10116.ENSRNOP00000011300.

    Chemistry

    BindingDBi O35240.
    ChEMBLi CHEMBL5757.

    Protein family/group databases

    TCDBi 1.A.6.1.2. the epithelial na(+) channel (enac) family.

    PTM databases

    PhosphoSitei O35240.

    Proteomic databases

    PRIDEi O35240.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000011300 ; ENSRNOP00000011300 ; ENSRNOG00000008380 .
    GeneIDi 286920.
    KEGGi rno:286920.

    Organism-specific databases

    CTDi 9311.
    RGDi 708578. Asic3.

    Phylogenomic databases

    eggNOGi NOG262945.
    GeneTreei ENSGT00640000091217.
    HOGENOMi HOG000247010.
    HOVERGENi HBG004150.
    InParanoidi O35240.
    KOi K04830.
    OMAi TECHMEC.
    OrthoDBi EOG72VH5P.
    PhylomeDBi O35240.
    TreeFami TF330663.

    Enzyme and pathway databases

    Reactomei REACT_198302. Stimuli-sensing channels.

    Miscellaneous databases

    NextBioi 625060.
    PROi O35240.

    Gene expression databases

    Genevestigatori O35240.

    Family and domain databases

    InterProi IPR004724. EnaC.
    IPR001873. Na+channel_ASC.
    IPR020903. Na+channel_ASC_CS.
    [Graphical view ]
    PANTHERi PTHR11690. PTHR11690. 1 hit.
    Pfami PF00858. ASC. 1 hit.
    [Graphical view ]
    PRINTSi PR01078. AMINACHANNEL.
    TIGRFAMsi TIGR00859. ENaC. 1 hit.
    PROSITEi PS01206. ASC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons."
      Waldmann R., Bassilana F., de Weille J.R., Champigny G., Heurteaux C., Lazdunski M.
      J. Biol. Chem. 272:20975-20978(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    2. "A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells."
      Lingueglia E., de Weille J.R., Bassilana F., Heurteaux C., Sakai H., Waldmann R., Lazdunski M.
      J. Biol. Chem. 272:29778-29783(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ASIC1.
      Strain: Wistar.
      Tissue: Brain.
    3. Cited for: TISSUE SPECIFICITY.
    4. "The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore."
      Coscoy S., de Weille J.R., Lingueglia E., Lazdunski M.
      J. Biol. Chem. 274:10129-10132(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF VAL-20; PHE-21 AND THR-26.
    5. "Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+."
      Babinski K., Catarsi S., Biagini G., Seguela P.
      J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors."
      Voilley N., de Weille J.R., Mamet J., Lazdunski M.
      J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, INHIBITION BY DRUGS.
    7. "Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons."
      Immke D.C., McCleskey E.W.
      Nat. Neurosci. 4:869-870(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY LACTATE, FUNCTION.
    8. "Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF."
      Catarsi S., Babinski K., Seguela P.
      Neuropharmacology 41:592-600(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY NPFF.
    9. "Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons."
      Sutherland S.P., Benson C.J., Adelman J.P., McCleskey E.W.
      Proc. Natl. Acad. Sci. U.S.A. 98:711-716(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels."
      Mamet J., Baron A., Lazdunski M., Voilley N.
      J. Neurosci. 22:10662-10670(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    11. "Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system."
      Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.
      Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    12. "How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons."
      Mamet J., Lazdunski M., Voilley N.
      J. Biol. Chem. 278:48907-48913(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE, INDUCTION BY NGFB.
    13. "Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade."
      Immke D.C., McCleskey E.W.
      Neuron 37:75-84(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY LACTATE AND CALCIUM.
    14. "Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability."
      Deval E., Baron A., Lingueglia E., Mazarguil H., Zajac J.-M., Lazdunski M.
      Neuropharmacology 44:662-671(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons."
      Diochot S., Baron A., Rash L.D., Deval E., Escoubas P., Scarzello S., Salinas M., Lazdunski M.
      EMBO J. 23:1516-1525(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY APETX2 TOXIN.
    16. "ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1."
      Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M.
      J. Biol. Chem. 279:19531-19539(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THR-40 AND SER-523, PHOSPHORYLATION AT THR-40 AND SER-523.
    17. "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current."
      Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.
      J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DLG4, SUBCELLULAR LOCATION.
    18. Cited for: FUNCTION, INTERACTION WITH STOM, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiASIC3_RAT
    AccessioniPrimary (citable) accession number: O35240
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 13, 2005
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 104 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Potentiated by FMRFamide-related neuropeptides By similarity. Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.By similarity

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3